We plan to extend our dose-ranging trial of N-acetylprocainamide (NAPA) by administering this drug to patients on a chronic basis. Chronic NAPA administration almost certainly will be needed to determine whether this compound also causes the systemic lupus erythematosus-like reaction that occurs in patients treated with procainamide (PA). Attempts to obtain this critical information indirectly in PA treated patients by correlating acetylator phenotype with the development of positive antinuclear antibody titers have yielded conflicting results. One explanation of this controversy is that a metabolite formed from PA is responsible for the reaction. Since fast and slow acetylators treated with PA have plasma PA concentrations that are not significantly different, this hypothesis would account for a similar incidence of this reaction in the two phenotypes. If this were the case, patients could receive long-term NAPA therapy without the risk of this side-effect because deacetylation of NAPA to PA occurs to only a minor extent, accounting for approximately 2% of total NAPA elimination in normal subjects. The mechanism by which PA causes the SLE-like reaction will also be of obvious interest. We will begin by attempting to identify hitherto unknown metabolites of PA that might be responsible for this reaction. It is expected that non-destructive analytical methods will be required to isolate and quantify these compounds, and we plan to begin by using HPLC. BIBLIOGRAPHIC REFERENCES: Lee, W.-K., Strong, J.M., Kehoe, R.F., Dutcher, J.S. and Atkinson, A.J., Jr.: Antiarrhythmic efficacy of N-acetylprocainamide in patients with premature ventricular contractions. Clin. Pharmacol. Ther. 19: 508-514, 1976. Atkinson, A.J., Jr., Krumlovsky, F.A., Huang, C.M., and del Greco, F.: Hemodialysis for severe procainamide toxicity: Clinical and pharmacokinetic observations. Clin. Pharmacol. Ther. 20: 585-592, 1976.